3 years ago

Zwitterionic hydrophilic interaction liquid chromatography-tandem mass spectrometry with HybridSPE-precipitation for the determination of intact cisplatin in human plasma

Zwitterionic hydrophilic interaction liquid chromatography-tandem mass spectrometry with HybridSPE-precipitation for the determination of intact cisplatin in human plasma
Cisplatin is a first-line chemotherapeutic for the treatment of a wide variety of cancers since its discovery in the 1960s. Although various techniques have been reported for the measurement of total platinum in biological matrices, such as inductively coupled plasma-mass spectrometry and derivatization procedures, a specific, sensitive and robust assay for the quantification of intact cisplatin is still lacking. Therefore, we present a rapid, selective, sensitive, and reliable UHPLC-MS/MS based method for the determination of intact cisplatin in human plasma in support of a Phase II clinical trial. The optimal chromatographic behavior of cisplatin was achieved on a Syncronis HILIC column (50 × 2.1mm, 1.7µm, zwitterionic stationary phase). The retention behavior of cisplatin on this zwitterion-based stationary phase was well described by an adsorptive interaction model. A simple sample preparation based on protein precipitation combined with the removal of phospholipids by HybridSPE-precipitation was developed. The method was proven to be free of a relative matrix effect. The assay was validated within a range of 20 − 10,000ng/mL using 100μL of plasma sample. The intra and inter-day precisions were all less than 7.6%, and none of the bias was greater than 13.1%, thus corroborating that the developed method is precise and accurate. As a proof of concept, the assay has been successfully applied to plasma samples obtained from different patients who were enrolled in the Phase II trial and were treated with cisplatin.

Publisher URL: www.sciencedirect.com/science

DOI: S003991401730632X

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